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Chapter 11

Chapter 11. Cell Communication. Overview: The Cellular Internet Cell-to-cell communication Is absolutely essential for multicellular organisms. Biologists Have discovered some universal mechanisms of cellular regulation. Figure 11.1.

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Chapter 11

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  1. Chapter 11 Cell Communication

  2. Overview: The Cellular Internet • Cell-to-cell communication • Is absolutely essential for multicellular organisms

  3. Biologists • Have discovered some universal mechanisms of cellular regulation Figure 11.1

  4. I. External signals are converted into responses within the cell • Evolution of Cell Signaling • Yeast cells • Activate mates by cell signaling • Causes cells to grow towards each other and eventually fuse • Signal transduction pathways • Convert signals on a cell’s surface into cellular responses • Are similar in microbes and mammals, suggesting an early origin

  5. I. External signals are converted cont… C. Local and Long-Distance Signaling • Direct Contact Signalling • Exchange substances through cell junctions • Cell-cell contact via membrane bound surface molecules. • Local Regulators • Secretion of chemical messengers. • Affect cells in the vicinity, not just in contact. 1) Stimulation by growth factors known as paracrine signalling.

  6. I. External signals are converted cont… C. Local and Long-Distance Signaling • Local Regulators cont. • Synaptic signalling • Occurs in nervous system • Electrical signal triggers the secretion of a neurotransmitter between nerve cells. • Long Distance Regulators • Affect cells in different parts of the body • Travel via circulatory system in animals • Hormones 1) Endrocrine signaling in animals

  7. The Three Stages of Cell Signaling: A Preview D. Earl W. Sutherland • Discovered how the hormone epinephrine acts on cells • Causes the release of glycogen (sugar) and its conversion to glucose • Discovered that epinephrine would only stimulate the glycogen converting enzyme when it was inside a cell. • Epinephrine plus the enzyme in a test tube didn’t work. • Sutherland suggested that cells receiving signals went through three processes • Reception • Transduction • Response

  8. EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 2 3 Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11.5 • Overview of cell signaling

  9. II. Reception: A signal molecule binds to a receptor protein, causing it to change shape • Basic Info • Cell signaling molecules bind to a receptor on the surface of the receiving cell. • This binding is shape specific. • Often a conformational (shape change) in the receptor protein occurs. • Receptors

  10. II. Reception: A signal molecule binds to a receptor protein, cont… • Intracellular receptors • Are cytoplasmic or nuclear proteins • The signal molecules are small or hydrophobic • can readily cross the plasma membrane use these receptors • Ex: Testosterone Receptors a) Once receptor binds testosterone, receptor enters nucleus and activates certain genes

  11. II. Reception: A signal molecule binds to a receptor protein, cont… • Receptors in the Plasma Membrane • three main types • G-protein-linked • Tyrosine kinases • Ion channel

  12. G-protein-linked receptors (pg 211 IMPORTANT) 7 transmembrane alpha-helices

  13. Receptor tyrosine kinases (Pg 212 – important)

  14. Ion channel receptors (pg 213 important too) Ligand?

  15. III. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Multistep pathways • Can amplify a signal • Provide more opportunities for coordination and regulation • Protein Phosphorylation & Dephosphorylation • Kinases add phosphate groups to proteins, usually activating them • Phosphatases remove phosphate groups from proteins, usually inactivating them.

  16. Pg. 215

  17. Small Molecules and Ions as Second Messengers • Are small, nonprotein, water-soluble molecules or ions • Spread through the cell by diffusion. • Most used: cyclicAMP (cAMP) and Ca2+

  18. NH2 NH2 NH2 N N N N N N N N N N N O O O N O Adenylyl cyclase Phoshodiesterase CH2 O HO Ch2 P –O O P O P P O CH2 O O O O O O O O O P Pyrophosphate H2O O O P P i OH OH OH OH OH ATP Cyclic AMP AMP Figure 11.9 • Cyclic AMP and epinephrine • ATP converted to cAMP by adenylyl cyclase protein in membrane • Causes a quick increase in cAMP in cytoplasm • Without ephinephrine, cAMP concentrations drop quickly due to cAMP being converted to AMP by phosphodiesterase inactivating it.

  19. Many G-proteins • Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways • cAMP often activates protein kinase A Read info on cholera Figure 11.10

  20. First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein GTP G-protein-linked receptor ATP cAMP Protein kinase A Cellular responses

  21. Calcium ions and Inositol Triphosphate (IP3) • Ca2+ even more common that cAMP as a 2nd messenger • Works as a 2nd messenger b/c low conc. of it in the cell. • Some Effects of increased conc. of Ca2+ • Muscle contractions • Secretion of substances • cell division • IP3 or diacylglycerol (DAG) are 2nd messengers which cause the release of Ca2+ from the ER

  22. Fig 11-13

  23. IV. Response: Cell signaling leads to regulation of cytoplasmic activities or transcription • Nuclear and Cytoplasmic Responses • Often a gene is turned on or off in response to the cell signaling. • Control of protein production • Protein activity in cytosol can be affected. • Other effects • Cell shape changes (read about yeast on pg 220)

  24. Fine-Tuning of the Response • Signal pathways with multiple steps • Can amplify the signal and contribute to the specificity of the response • Each step activates multiple copies of the following step • Provides different points where the cell’s response can be regulated.

  25. Signalmolecule Plasmamembrane Receptor Threedifferentproteinkinases Scaffoldingprotein Figure 11.16 • Scaffolding proteins • can increase the signal transduction efficiency • Holds multiple proteins together that interact during the signaling process.

  26. Wiskott-Aldrich Syndrome • Caused by the absence of a single relay protein (WAS Protein). • The WAS protein is located just beneath the cell surface a) it interacts with the microfilaments of the cytoskeleton • When the WAS protein is absent, the cytoskeleton is not properly organized and signaling pathways are disrupted.

  27. Termination of the Signal • Signal response is terminated quickly • By the reversal of ligand binding 1) Lack of binding stop the signaling process.

  28. V. Apoptosis • Cell death in C. elegans • Cell death necessary during worm development. • Cell death enzymes are called caspases • Two proteins involved Ced-3 and Ced-4 • Proteins present in all cells, but in inactive form. • Ced-9 is a protein in the mitochondria membrane and binds Ced-4, inactivating it • Signal causes Ced-9 to release Ced-4 and Ced-4 activates Ced-3 and cell death occurs.

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